CYP4X1

Chr 1

cytochrome P450 family 4 subfamily X member 1

Also known as: CYPIVX1

NCBI Gene: 260293 ENSG00000186377 UniProt: Q8N118 OMIM: 614999

The protein is a cytochrome P450 monooxygenase that catalyzes epoxidation of anandamide's arachidonoyl moiety, potentially modulating endocannabinoid signaling in the brain. The gene shows very low constraint against loss-of-function variants (pLI near zero, LOEUF >1), and no clear human disease associations have been established despite its suggested role in neurovascular function. Clinical significance of CYP4X1 variants in pediatric neurological conditions remains uncertain.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the cytochrome P450 superfamily of enzymes and is located within a cluster of genes belonging to this superfamily on chromosome 1. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The expression pattern of a similar rat protein suggests that this protein may be involved in neurovascular function in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.11

Clinical Summary— CYP4X1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

70 VUS of 82 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.11LOEUF

pLI 0.000

Z-score 1.12

OE 0.77 (0.54–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.29Z-score

OE missense 0.78 (0.70–0.88)

220 obs / 280.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.54–1.11)

0≤0.351.4

Missense OE?0.78 (0.70–0.88)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 21 / 27.3Missense obs/exp: 220 / 280.7Syn Z: 0.28

This gene — mechanism propensity

0.75top 25%

GOF

0.6247th %ile

LOF

0.2582th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	70	70
Likely Benign	5	5
Benign	0	0
Total	75	75

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap CYP4X1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →